Previous work has shown that the transport of weak electrolytes across the wall of the small intestine can be described in terms of a model system of three compartments in series, in which the pH of the intermediate compartment is greater than that of the bulk phases. This project is concerned with three areas of investigation associated with this transport system: (a) Consideration of the theoretical bases of weak electrolyte transport with the objectives of defining the parameters of weak electrolyte movement in biological systems, and of developing procedures for the evaluation of these parameters. (b) Evaluation of the parameters of weak electrolyte transport in biological systems, with the objective of identifying the determinants of weak electrolyte permeability in physicochemical terms. (c) Investigation of the mechanisms of asymmetric acid-base metabolism that are fundamental to the generation of compartments of distinctive pH, and to the function of the three compartment system for weak electrolyte transport.